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6 results on '"Andrea Tarlton"'

1. Memory-like innate response to booster vaccination with MF-59 adjuvanted influenza vaccine in children

Author

Dmitri Kazmin, Elizabeth A. Clutterbuck, Giorgio Napolitani, Amanda L. Wilkins, Andrea Tarlton, Amber J. Thompson, Emmanuele Montomoli, Guilia Lapini, Smiti Bihari, Rachel White, Claire Jones, Matthew D. Snape, Ushma Galal, Ly-Mee Yu, Rino Rappuoli, Giuseppe Del Giudice, Andrew J. Pollard, and Bali Pulendran

Subjects
Immunologic diseases. Allergy, RC581-607, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract The pediatric population receives the majority of vaccines globally, yet there is a paucity of studies on the transcriptional response induced by immunization in this special population. In this study, we performed a systems-level analysis of immune responses to the trivalent inactivated influenza vaccine adjuvanted with MF-59 in children (15–24 months old) and in young, healthy adults. We analyzed transcriptional responses elicited by vaccination in peripheral blood, as well as cellular and antibody responses following primary and booster vaccinations. Our analysis revealed that primary vaccination induced a persistent transcriptional signature of innate immunity; booster vaccination induced a transcriptional signature of an enhanced memory-like innate response, which was consistent with enhanced activation of myeloid cells assessed by flow cytometry. Furthermore, we identified a transcriptional signature of type 1 interferon response post-booster vaccination and at baseline that was correlated with the local reactogenicity to vaccination and defined an early signature that correlated with the hemagglutinin antibody titers. These results highlight an adaptive behavior of the innate immune system in evoking a memory-like response to secondary vaccination and define molecular correlates of reactogenicity and immunogenicity in infants.

Published
2023
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2. PemBla: A Phase 1 study of intravesical pembrolizumab in recurrent non‐muscle‐invasive bladder cancer

Author

Victoria K. Woodcock, Ji‐Li Chen, Karin Purshouse, Chrissie Butcher, Linda Collins, Caroline Haddon, Gillian Verrall, Leena Elhussein, Corran Roberts, Andrea Tarlton, Margarida Rei, Giorgio Napolitani, Mariolina Salio, Mark R. Middleton, Vincenzo Cerundolo, Jeremy Crew, and Andrew S. Protheroe

Subjects
bladder cancer, checkpoint inhibition, immunotherapy, intravesical, Phase 1, Diseases of the genitourinary system. Urology, RC870-923
Abstract

Abstract Objectives This study aimed to investigate the anti‐PD‐1 inhibitor pembrolizumab as a potential agent for use in non‐muscle‐invasive bladder cancer (NMIBC) by conducting a Phase 1 safety run‐in study to assess the safety and tolerability of intravesical pembrolizumab after transurethral resection of the bladder tumour (TURBT). Patients and methods Eligible patients had recurrent NMIBC for which adjuvant treatment post TURBT was a reasonable treatment option, Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0–1 and adequate end‐organ function. Pembrolizumab was administered by intravesical instillation once weekly for a total of six doses. Intra‐patient dose escalation was performed in three paired patient cohorts with doses starting at 50 mg and increasing through 100 mg to a maximum of 200 mg. Adverse events (AEs) were assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.03 with dose limiting toxicity (DLT) defined as a clinically significant, drug‐related, Grade 4 haematological or Grade 3 or higher non‐haematological toxicity occurring within 7 days of administration of the first treatment at a given dose for that patient. Results Six patients were treated with no DLTs seen during dose escalation. Drug‐related AEs were of low grade and included dysuria and fatigue. All patients completed six doses of treatment as planned. Pharmacokinetic and pharmacodynamic assays did not detect any pembrolizumab in the serum following repeated intravesical administration, and no changes in peripheral immune cell populations were observed. Conclusions Administration of intravesical pembrolizumab was well tolerated and did not raise any safety concerns in patients with NMIBC following TURBT. There was no evidence of systemic absorption or systemic immune effects following intravesical administration. Further studies are required to assess whether intravesical administration has anti‐tumour activity.

Published
2023
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3. NY-ESO-1 specific antibody and cellular responses in melanoma patients primed with NY-ESO-1 protein in ISCOMATRIX and boosted with recombinant NY-ESO-1 fowlpox virus

Author

Linda Pan, Lloyd L. Old, Vincenzo Cerundolo, Paul Nathan, Abdelouahid Tajar, Mark R. Middleton, Christian H. Ottensmeier, Judy Browning, Christian Verfaille, Jonathan Cebon, Sacha Gnjatic, Ji-Li Chen, Douglas G. Altman, Sarah Pratap, Ioannis Karydis, Andrea Tarlton, Amina Dawoodji, and Ralph Venhaus

Subjects
Fowlpox, Cancer Research, Melanoma, T cell, Heterologous, Biology, medicine.disease, Virology, Fowlpox virus, Vaccination, medicine.anatomical_structure, Oncology, Immunology, medicine, NY-ESO-1, CD8
Abstract

Vaccination strategies based on repeated injections of NY-ESO-1 protein formulated in ISCOMATRIX particles (NY-ESO-1 ISCOMATRIX) have shown to elicit combined NY-ESO-1 specific antibody and T cell responses. However, it remains unclear whether heterologous prime-boost strategies based on the combination with NY-ESO-1 ISCOMATRIX with different NY-ESO-1 boosting reagents could be used to increase NY-ESO-1 CD8(+) or CD4(+) T cell responses. To address this question, we carried out a randomized clinical trial in 39 high-risk, resected melanoma patients vaccinated with NY-ESO-1 ISCOMATRIX, and then boosted with repeated injections of either recombinant fowlpox virus encoding full length NY-ESO-1 (rF-NY-ESO-1) (Arm A) or NY-ESO-1 ISCOMATRIX alone (Arm B). We have comprehensively analyzed NY-ESO-1 specific T cells and B cells response in all patients before and after vaccination for a total of seven time points per patient. NY-ESO-1 ISCOMATRIX alone elicited a strong NY-ESO-1 specific CD4(+) T cell and antibody response, which was maintained by both regiments at similar levels. However, CD8(+) T cell responses were significantly boosted in 3 out of 18 patients in Arm A after the first rF-NY-ESO-1 injection and such responses were maintained until the end of the trial, while no patients in Arm B showed similar CD8(+) T cell responses. In addition, our results clearly identified immunodominant regions in the NY-ESO-1 protein: NY-ESO-179-102 and NY-ESO-1115-138 for CD4+ T cells and NY-ESO-185-108 for CD8+ T cells in a large proportion of vaccinated patients. These regions of NY-ESO-1 protein should be considered in future clinical trials as immunodominant epitopes.

Published
2014

4. 3353 Seropositivity to tumour antigens as a potential new biomarker for melanoma relapse

Author

Andrea Tarlton, Paul Nathan, Christian H. Ottensmeier, Ann Petruckevitch, Mark R. Middleton, Rohini Sharma, H. Hepburne-Scott, P. Bonner, L L Clark, Kevin A. Myers, and O. Bassett

Subjects
Cancer Research, Oncology, Antigen, business.industry, Melanoma, Immunology, Medicine, Biomarker (medicine), business, medicine.disease
Published
2015

5. Seropositivity to tumour antigens as a potential new biomarker for melanoma relapse

Author

Ottensmeier Chh., Rohini Sharma, Mark R. Middleton, O. Bassett, L L Clark, H. Hepburne-Scott, Paul Nathan, Andrea Tarlton, Kevin A. Myers, Ann Petruckevitch, and P. Bonner

Subjects
Oncology, Cancer Research, medicine.medical_specialty, business.industry, Melanoma, Stage ii, medicine.disease, Antigen, Immunity, Internal medicine, Immunology, Biomarker (medicine), Medicine, business
Abstract

e20049 Background: Current prognostic markers fail to identify many patients with stage II / III melanoma who go on to relapse. Immunity has been assumed to play a part in influencing risk of recur...

Published
2015

6. A Ufd2/D4Cole1e chimeric protein and overexpression of Rbp7 in the slow Wallerian degeneration (WldS) mouse

Author

Laura Conforti, E. Anne Buckmaster, Weiqian Mi, Till G. A. Mack, Diana Wagner, Andrea Tarlton, Michael Coleman, and V. Hugh Perry

Subjects
Central Nervous System, Wallerian degeneration, DNA, Complementary, Saccharomyces cerevisiae Proteins, Protein family, Recombinant Fusion Proteins, Mutant, Molecular Sequence Data, Chimeric gene, Biology, Ubiquitin-conjugating enzyme, Fungal Proteins, Exon, Mice, Peripheral Nervous System, medicine, Animals, Amino Acid Sequence, Nicotinamide-Nucleotide Adenylyltransferase, RNA, Messenger, Gene, Multidisciplinary, Base Sequence, Sequence Homology, Amino Acid, Proteins, Retinol-Binding Proteins, Cellular, Exons, Biological Sciences, medicine.disease, Fusion protein, Molecular biology, Mice, Inbred C57BL, Retinol-Binding Proteins, Ubiquitin-Conjugating Enzymes, Wallerian Degeneration
Abstract

Exons of three genes were identified within the 85-kilobase tandem triplication unit of the slow Wallerian degeneration mutant mouse, C57BL/ Wld S . Ubiquitin fusion degradation protein 2 ( Ufd2 ) and a previously undescribed gene, D4Cole1e , span the proximal and distal boundaries of the repeat unit, respectively. They have the same chromosomal orientation and form a chimeric gene when brought together at the boundaries between adjacent repeat units in Wld S . The chimeric mRNA is abundantly expressed in the nervous system and encodes an in-frame fusion protein consisting of the N-terminal 70 amino acids of Ufd2 , the C-terminal 302 amino acids of D4Cole1e , and an aspartic acid formed at the junction. Antisera raised against synthetic peptides detect the expected 43-kDa protein specifically in Wld S brain. This expression pattern, together with the previously established role of ubiquitination in axon degeneration, makes the chimeric gene a promising candidate for Wld . The third gene altered by the triplication, Rbp7 , is a novel member of the cellular retinoid-binding protein family and is highly expressed in white adipose tissue and mammary gland. The whole gene lies within the repeat unit leading to overexpression of the normal transcript in Wld S mice. However, it is undetectable on Northern blots of Wld S brain and seems unlikely to be the Wld gene. These data reveal both a candidate gene for Wld and the potential of the Wld S mutant for studies of ubiquitin and retinoid metabolism.

Published
2000

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